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2006 IN REVIEW: Now the center of attention, DNA’s little sister

L.A. Cicero

Two days after winning the Nobel Prize in Medicine or Physiciology, Andrew Fire (right) congratulates med school colleague Roger Kornberg (left) for winning the prize in chemistry.

BY MITZI BAKER

For years RNA received second billing to its flashier big sister, DNA. But this was the year that it got asked to the prom: Two Nobel Prizes were awarded for basic research involving RNA.

The central dogma of genetics holds that double-stranded DNA makes single-stranded messenger RNA, which in turn makes protein. While there has been much hoopla for decades about research focusing on the DNA gene rather than the RNA message, this year RNA became the hot ticket, with two members of the medical school faculty winning separate Nobel Prizes for their complementary work in this area. One was awarded for work elucidating how RNA turns genes on, while the other was for an explanation of a mechanism to turn them off.

The Nobel Prize in Chemistry was for work that showed how DNA is converted into RNA through a process known as transcription, using the enzyme RNA polymerase. The winner, professor of structural biology Roger Kornberg, PhD, was recognized for his success in charting the complex arrangement of the 30,000 atoms in the RNA polymerase. "This allows us for the first time to see the chemical details of transcription," Lars Thelander, a Nobel panel member, told National Geographic. "It has many implications for human diseases, antibiotics, stem cells and so on."

The Nobel Prize in Physiology or Medicine went to pathology professor Andrew Fire, PhD, and Craig Mello, PhD, of University of Massachusetts, for explaining an oddity—double-stranded RNA. They showed that it can destroy a messenger RNA with a matching sequence, halting the orderly progression of DNA to RNA to protein. The process is now known as RNA interference, or RNAi. "It was like opening the blinds in the morning," Erna Moller, another Nobel committee member, told the Associated Press. "Suddenly you can see everything clearly."

These RNA discoveries have yet to produce any direct clinical benefits for patients. But researchers are captivated by their enormous potential, and their enthusiasm has begun to filter into the public's general knowledge of science. And there's reason to believe that the discoveries will eventually have a direct effect on medical care. Indeed, in only eight years since the RNAi gene-silencing mechanism was first announced, therapeutics based on it have entered clinical trials, including treatments for macular degeneration, respiratory syncytial virus and hepatitis C.

And at least one big pharmaceutical company is betting on RNAi's prospects: At the end of October, Merck spent $1.1 billion to acquire San Francisco-based Sirna Therapeutics, one of the leading developers of RNAi-based therapies.